Understanding intelligence-related variations in electroencephalographic (EEG) activity requires advanced mathematical approaches capable of capturing geometric transformations and long-range dependencies in neural dynamics. These approaches may provide methodological advantages over conventional spectral and connectivity-based techniques by offering deeper insights into the structural and functional organization of neural networks. In this study, we integrate Clifford algebra, Noether’s theorem and fractional calculus to analyze EEG signals from high- and low-IQ individuals, looking for key intelligence-related differences in cortical organization. Clifford algebra enables the representation of EEG signals as multivectors, preserving both magnitude and directional relationships across cortical regions. Noether’s theorem provides a quantitative measure of symmetry properties linked to spectral features, identifying conserved functional patterns across distinct brain regions. Mittag-Leffler functions, derived from fractional calculus, characterize long-range dependencies in neural oscillations, allowing for the detection of memory effects and scale-invariant properties often overlooked by traditional methods. We found significant differences between high- and low-IQ individuals in geometric trajectories, hemispheric connectivity, spectral properties and fractional-order dynamics. High-IQ individuals exhibited increased spectral asymmetry, enhanced spectral differentiation, distinct geometric trajectories and greater fractional connectivity, particularly in frontal and central regions. In contrast, low-IQ individuals displayed more uniform hemispheric connectivity and heightened fractional activity in occipital areas. Mittag-Leffler fractional exponents further indicated that high-IQ individuals possessed more varied neural synchronization patterns. Overall, our multi-faceted approach suggests that intelligence-related neural dynamics are characterized by an asymmetric, functionally specialized and fractionally complex cortical organization. This results in significant differences in network topology, efficiency, modularity and long-range dependencies.

This work establishes a revolutionary synthesis between quantum optimization and psychodynamic theory through two groundbreaking innovations:  1. Quantum Harmonic Countermodulation Optimization++ (Q-HCMO++)}: A topological quantum algorithm achieving 99.4\% success rate under 18.2 dB noise through σz⊗σz couplings............2. Projection Sphere Model (PSM)}: A 6-layer quantum psychodynamic framework revealing fractal projection patterns .......... with 92.3\% accuracy in predicting 50-year political cycles.  

There are more and more individuals with hypertension in the globe. How to manage and self-manage hypertension with better cost-effectiveness needs economic principles and theories. Herein, in this article, the author suggests to develop a new discipline on economics and hypertension. The author briefly introduces the current status of hypertension in both China and the globe. Since lifestyle links to economics and hypertension, the author proposes that it’s about time to establish the “economics of hypertension” because it contributes to better management and self-management of hypertension not only in China but also in the globe. In fact, many clinical studies and trials have already confirmed the benefits of economic knowledge on management and self-management of hypertension. When people understand and know about related economic principles and theories, they will get more benefits from Economics of Hypertension and better protection of blood pressure with cost-effectiveness. All in all, it’s about time to establish the Economics of Hypertension, since it contributes to better management and self-management of hypertension with better cost-effectiveness. Just like Health in All Policies and Health in All Laws, Health in All Economics should be a novel consensus in the new era, particularly the COVID-19 pandemic and post-COVID-19 era.

Isolated splenic metastasis from colorectal cancer (CRC) is extremely rare, occurring in only 1.2–7.1% of cases, due to the spleen’s strong immune surveillance, lack of afferent lymphatic drainage, and unique blood flow. While metastasis typically spreads to the liver and lungs, haematogenous dissemination to the spleen can occur, though the exact mechanism remains unclear. Most cases are asymptomatic and discovered incidentally through imaging or rising carcinoembryonic antigen (CEA) levels. Treatment options include systemic chemotherapy, splenectomy, or a combination, depending on disease extent and patient condition. This study reports two cases of sigmoid colon adenocarcinoma initially treated with curative surgery and six months of FOLFOX chemotherapy. Both patients showed no initial metastasis but later presented with rising CEA levels (140 ng/mL). CT scans revealed isolated splenic metastases without other systemic involvement. They underwent an additional six months of chemotherapy, achieving stable disease with no complications. These cases highlight the importance of close surveillance and suggest that systemic chemotherapy alone may be a viable alternative to splenectomy in select patients.

Rationale: The isotopic composition of dissolved dinitrogen gas (δ 15N-N 2) in water can offer a powerful constraint on the sources and pathways of nitrogen cycling in aquatic systems. However, due to the large presence of atmosphere-derived dissolved N 2 in these systems, high-precision (order-0.001‰) measurements of N 2 isotopes paired with inert gas measurements are required to disentangle atmospheric and biogeochemical signals. Additionally, the solubility equilibrium isotope fractionation of N 2 and its temperature and salinity dependence are underconstrained at this level of precision. Methods: We introduce a new technique for sample collection, processing, and dynamic dual-inlet mass spectrometry allowing for high-precision measurement of δ 15N-N 2 and δ(N 2/Ar) with simultaneous measurement of δ( 40Ar/ 36Ar) and δ(Kr/N 2) in water. We evaluate the reproducibility of this technique and employ it to redetermine the solubility equilibrium isotope effects for dissolved N 2 across a range of temperatures and salinities. Results: Our technique achieves measurement reproducibility (1σ) for δ 15N-N 2 (0.006‰) and δ(N 2/Ar) (0.41‰) suitable for tracing biogeochemical nitrogen cycling in aquatic environments. Through a series of air-water equilibration experiments, we find a N 2 solubility equilibrium isotope effect [ε=α/1000–1; where α=( 29N 2/ 28N 2) dissolved/( 29N 2/ 28N 2) gas] in water of ε(‰)=0.753–0.004•T [where T is temperature (°C)], with uncertainties of order-0.001‰ over the temperature range of ~2-23°C and salinity range of ~0-30 psu. We find no apparent dependence of ε on salinity. Conclusions: Our new method allows for high-precision measurements of the isotopic composition of dissolved N 2 and Ar, and dissolved N 2/Ar and Kr/N 2 ratios, within the same sample. Pairing measurements of N 2 with inert gases facilitates quantification of excess N 2 from biogeochemical sources and its isotopic composition. This method allows for a wide range of applications in marine, coastal, and freshwater environments to characterize and quantitatively constrain potential nitrogen cycling sources and pathways and to differentiate between physical and biological isotope signals in these systems.

Title pageManuscript TitleDifferential Response of Nail Psoriasis to IL-17 Inhibitors: A Case Reportauthor nameDong Jiang, Yu Lu, Yi-Yu Guo, Jin-Hong Ge, Yun-Peng Gao, Deng-Ke Yangauthor affiliation：Department of Dermatology, Kunming Municipal Hospital of Traditional Chinese Medicine , Kunming, 650011, People’s Republic of ChinaCorrespondceDeng-Ke Yang, Department of Dermatology, Kunming Municipal Hospital of Traditional Chinese Medicine, No. 2628 of Xiangyuan Street, Chengong District, Kunming,650011,Yunnan Province, People’s Republic of China, Tel +86 15877974436, Email 523687402@qq.comFundingNo sources of funding were declared for this study.Conflict of InterestNone declared.AuthorshipDong Jiang participated in the conceptualization of the study and was responsible for writing the original draft.Yu Lu was involved in the conceptualization process, contributing ideas and perspectives that helped shape the overall direction of the study.Yi-Yu Guo provided the necessary resources, which include access to research materials, equipment, or data sources that were crucial for the execution of the study.Jin-Hong Ge carried out the investigation, through fieldwork, data collection to gather information relevant to the study.Yun-Peng Gao was in charge of visualization to present the data and findings in a more accessible way.Deng-Ke Yang supervised the entire study, ensuring that the research was conducted in accordance with the established goals and ethical standards. Additionally, Deng - Ke Yang reviewed and edited the manuscript, providing valuable feedback to improve the quality and clarity of the written work.All authors reviewed and approved the final manuscript.ConsentWritten consent has been obtained from the patient for the treatment of psoriasis with biological agents. And written permission to publish the patient’s case and photographs was acquired.Key Clinical MessageA female with moderate-to-severe plaque psoriasis and nail psoriasis demonstrated a discordant therapeutic response to two IL-17 inhibitors. Initial treatment with secukinumab achieved complete skin clearance by 12 weeks but showed no improvement in nail psoriasis until 30 weeks of use. Switching to ixekizumab resulted in rapid resolution of residual nail psoriasis disease alongside sustained cutaneous control, maintained through 24-month follow-up. This case highlights potential mechanistic differences between IL-17-targeted biologics in addressing psoriatic nail pathology.Keywords ：Psoriasis, Nail psoriasis, Biologics, Secukinumab, Ixekizumab

Fatigue damage to asphalt roads under cyclic loads affects traffic and regional development. The deterministic cumulative damage theory is an important tool for studying material fatigue damage. However, owing to the distribution characteristics of asphalt materials and the randomness in the fatigue damage process, the study of random damage is particularly important. Based on the cumulative damage theory of asphalt materials under repeated loads, the random distribution characteristics of asphalt pavement materials and the randomness of actual traffic loads were used to determine the optimal pavement life of asphalt pavement materials under different conditions. A damage model was created based on the probability density functions for various critical damage values and rates. They derived equations for the evolution of the expected fatigue damage and its variance under these conditions, as follows: When the traffic load follows a Poisson distribution, comparing the variability of fatigue damage under different fatigue life distributions to traffic load expectations reveals that a log-normal distribution with similar expected values and variances is suitable for lighter traffic, whereas a normal distribution with a significantly higher expected value than the variance is suitable for heavier traffic. Under the same cyclic fatigue load, the fatigue damage to the asphalt material can vary widely from the expected value. Traditional deterministic damage theories account for only part of this variation, explaining the diversity of parameters in engineering models. The study found that a critical damage value below 0.8 indicates that the material can handle less fatigue load, with little difference between 0.8 and 1. For a better road economy and longer fatigue life, asphalt should aim for a critical damage value of approximately 0.8. In addition, when the damage growth rate was close to 1, the asphalt fatigue damage increased at a slower rate. Finally, the theoretical pavement life calculated in this study was compared with the average maintenance years of actual asphalt pavements using an equivalent formula for traffic load and service life. The study concluded that the theory aligns with reality and that the optimal asphalt pavement service life derived from the random cumulative fatigue damage theory significantly exceeds the actual data.

Duffy null phenotype is common in people of African ancestry and is associated with lower baseline white blood cell (WBC) and neutrophil counts. We evaluated whether presence of the Duffy null phenotype had any association with neutropenia in our patients with sickle cell disease on hydroxyurea (HU). We found a statistically significant difference (p=0.006) in HU maximum tolerated dose (MTD) in patients with Duffy null phenotype compared with individuals who are Duffy positive. Our study suggests that careful dose escalation is warranted in those individuals who are Duffy null.

Background: Children treated with platinum chemotherapy agents such as cisplatin and carboplatin are at risk for developing irreversible sensorineural hearing loss. Carboplatin ototoxicity is less prevalent than cisplatin ototoxicity, except when used in high doses. Objective: We sought to investigate risk factors associated with ototoxicity in high dose carboplatin hematopoietic stem cell transplantation (cHSCT) in a pediatric population. Study Design: We accepted audiograms with a minimum requirement of threshold data at 4 kHz in at least one ear, allowing us to assess younger, more difficult to test patients and focus on hearing losses at important speech frequencies that can benefit from amplification. Eligible subjects underwent an autologous cHSCT at our institution from 1/1/2008 – 6/30/2022. Three audiologic outcome measures were evaluated – worsening in SIOP grade, significant change in hearing, and ototoxicity. Results: Forty-three cHSCTs from 29 patients had sufficient audiologic data. Logistic regression analysis revealed that cumulative dose of prior cisplatin (OR = 1.01, 95% CI = 1.002-1.014, p = 0.011), and cumulative dose of carboplatin in the preparative regimen (OR = 1.003, 95% CI = 1.001-1.004, p = 0.001), were associated with ototoxicity. Concurrent furosemide with carboplatin administration resulted in 100% ototoxicity, with patients demonstrating a mean change in SIOP grades by 2.0 SE + .038. Conclusion: This report demonstrates that concomitant furosemide administration with carboplatin in cHSCT is associated with ototoxicity, made possible, using criterion that allowed for evaluation of very young children. Further investigations capturing very young patients is needed.

Metamorphosis is one of the major innovations in the evolutionary history of insect, playing an important role in environmental adaptation and biodiversity formation. However, it is still a challenge to recognize the underlying mechanisms of insect metamorphosis in traditional molecular biology. In this study, based on 138 insect genomes across 10 orders, we present a gene network classification model (GNCM) utilizes deep learning (DL) and attention mechanism (AM) to mine some key genes of metamorphosis. The GNCM identified a total of 97 sets of orthologous genes (OGs) with high weights in insect metamorphosis, and the subsequent annotations suggested that these genes were involved in hormone regulation, immune, detoxification, metabolism and developmental functions. Notably, 38 genes with high weights showed specific expression lever of their transcripts during the pupal stage. This study not only developed a new method of artificial intelligence for evolutionary biology, but also provides a new insight to understand the macroevolutionary of insect metamorphosis.

As the world transitions to sustainable energy, integrating solar power into electrical grids is critical. This article explores grid-connected solar projects, highlighting the vital role of PVsyst software in their design and analysis. PVsyst enables engineers to model complex solar systems, simulating effects like shading and fine-tuning parameters for optimal efficiency. By evaluating energy yield, losses, and performance ratio, PVsyst provides essential insights. Real-world case studies demonstrate solutions to common issues. Economic analysis tools assess return on investment. As grid-connected solar advances, PVsyst will likely evolve to enable more complex and sustainable applications. This software is pivotal in making solar a seamless part of our energy future

Demolition and removal of aging dam structures is increasingly common as a part of river restoration efforts, with anticipated benefits for re-establishing connectivity among river biota and habitats. We studied fish movement behavior in the vicinity of a run-of-river, low head dam before and after its removal. Radio telemetry was used to track movement of smallmouth bass and determine if movement past the dam site increased following removal. We also conducted a translocation experiment to confirm that habitat structure and flow condition at the restored site did not impede passage. Movement of radio-tagged smallmouth past the dam site was moderately different following dam removal, with a minor improvement in upstream passage. Results of translocation experiments indicated that the dam remnant site did not impede passage, as return rate of fish translocated past the dam was comparable to homing behavior observed in previous studies. We hypothesize that technological constraints combined with ontogenetic patterns in Smallmouth Bass spatial ecology reduced our likelihood of observing individual dispersal. In systems lacking migratory (e.g. diadromous) species, research to document effects of dam removal on fish movement and connectivity must consider how ontogenetic variation in movement behavior may limit our ability to observe and document ecological outcomes. A combination of approaches is likely to be most effective for studying non-migratory species responses to dam removal. Experimental translocation can be effective for confirming short-term improvements in fish passage, though other methods are more appropriate for documenting ecological benefits to fish populations and communities over longer timescales.

Gingival Squamous Cell Carcinoma: An Enigmatic Diagnostic ChallengeKey Clinical MessageThe similarities of Gingival Squamous Cell Carcinoma with common periodontal lesions could cause a delay in diagnosis or even a misdiagnosis. In cases with suspected gingival lesions, differential diagnosis of squamous cell carcinoma should always be considered because it can have a favorable prognosis, if the treatment is initiated early.AbstractOral squamous cell carcinoma (OSCC) is one of the highly invasive malignancies globally, accounting for the vast majority of all oral cancers, i.e., more than 90%. Carcinomas of the gingiva represent a distinct subgroup of OSCC, constituting approximately 12% of all OSCC cases. These neoplasms might mimic the inflammatory and reactive state of the periodontium, often leading to a delay in diagnosis and hence, poorer prognosis.An atypical case of gingival squamous cell carcinoma in a 48-year-old female patient has been reported here. The patient presented with a 3-month history of pain and burning sensation in the lower left back region of the jaw. Clinical examination showed a proliferative lesion extending from the marginal gingiva to the buccal vestibule adjacent to teeth 36 and 37. Given the clinical manifestations and differential diagnosis of infectious granulomatous lesions and malignant neoplasms, an excisional biopsy was performed and a diagnosis of well-differentiated squamous cell carcinoma was made. The patient was subsequently referred to the Oral and Maxillofacial Surgery Department for further treatment, which included surgical excision of the tumor with segmental mandibulectomy and selective neck dissection.Therefore, the lesion must be identified early, to start treatment, stop metastases, and enhance the prognosis.Keywords: Gingiva, malignancy, misdiagnosis, squamous cell carcinomaIntroductionAs the most common malignant neoplasm affecting the structures of the oral cavity, squamous cell carcinoma (SCC) accounts for over 90% of all oral malignant lesions [1]. The lateral/ventral aspect of the tongue and floor of the mouth are considered the most common sites for intraoral SCC, excluding the carcinoma of the lip vermilion (which has a different etiology) [2]. Gingival lesions comprise approximately 12% of all intraoral cases [1]. Compared to the maxilla, the mandible has a higher likelihood of having gingival SCC, most of which are located in the molar region [3]. However, gingival carcinoma is frequently diagnosed too late, or often misdiagnosed because it resembles common benign inflammatory lesions. Early-stage carcinoma can mimic an erosion, small ulcer, exophytic mass, or a periodontal lesion. They can also present as an asymptomatic erythematous or white lesion, or both [4]. So, when treating gingival lesions, especially in elderly patients, the SCC of the gingiva should be taken into account when making a differential diagnosis. To begin treatment early and improve the prognosis, it is imperative to diagnose gingival lesions as soon as possible.Here, we document a rare case of a 48-year-old female patient with gingival squamous cell carcinoma on the left mandibular posterior area.CASE HISTORY AND EXAMINATIONA 48-year-old female patient was presented at the Periodontics Department, with the chief complaint of pain and burning sensation on the lower left posterior region of the jaw for three months. The pain was spontaneous, continuous, severe in intensity, non-radiating type, aggravated on taking hot and spicy foods and touching while relieved on taking analgesics. Medical history was non-significant. There was no history of alcohol and tobacco abuse, both in smoked and smokeless form, and no positive family history of malignancy. According to the patient, she had visited a private dental clinic for the same problem, as soon as she started developing the clinical symptoms i.e., 3 months before reporting to our department. She mentioned that the sole intervention she received was oral prophylaxis followed by two courses of antibiotics (a combination of Amoxicillin and Metronidazole), as prescribed by a private dental practitioner. Since there was no improvement in the clinical symptoms, the patient was referred to our department.Upon extra-oral examination, a single, non-tender, mobile, and firm submandibular lymph node was palpated on the left side. Intra-oral examination revealed an ulcer-proliferative lesion extending from the marginal gingiva to the buccal vestibule, measuring approximately 15mm\(\times\ \)8mm  adjacent to teeth 36 and 37, with irregular necrotic margins (Figure 1). Uniformly white plaques were also evident, seen on the underlying vestibular fundus, as well as on the mesial attached gingiva adjacent to tooth 35. Intra-oral Periapical Radiograph (IOPAR) of the region revealed bone loss on the furcation area in relation to 36, while the interdental bone on both sides was intact (Figure 2). Complete blood investigations were done, which were within the normal range.DIFFERENTIAL DIAGNOSIS, INVESTIGATIONS AND TREATMENTIn view of the clinical manifestations, we made a differential diagnosis which included Squamous Cell Carcinoma (SCC), verrucous carcinoma, homogenous leukoplakia as well as Necrotizing Ulcerative Periodontitis (NUP). However, because of lesion’s persistence and poor responsiveness to medical therapy, NUP was excluded from the differential diagnosis and a strong suspicion of non-infectious and non-inflammatory disease was considered. Under local anesthesia, every visible part of the lesion was removed and sent for histopathological analysis. (Figure 3, 4)Histopathological examination revealed dysplastic keratinized stratified squamous epithelium overlying the fibro-cellular connective tissue stroma. The underlying stroma was infiltrated with tumor cells forming islands and sheets. The tumor cells showed dysplastic features such as increased cytoplasmic ratio, cellular and nuclear pleomorphism, anisocytosis, anisonucleosis, atypical mitotic figures, and abundant keratin pearl formation (Figure 5). Intense inflammatory cell infiltration comprising chiefly of lymphocytes and plasma cells was also noted. These microscopic features led to the final diagnosis of well-differentiated squamous cell carcinoma (TNM staging: T1N1M0,).T (Size of the primary tumor) – T1, because the size of the primary tumor was <2cmN (Regional lymph node involvement) – N1, because it was positive for lymph node level IB metastasisM (Distant metastasis) – M0, because of no distant metastasisThe patient was then referred to the Department of Oral and Maxillofacial Surgery for further treatment, where a wide local excision of the lesion with segmental mandibulectomy and selective neck dissection (lymph node level I-IV), followed by removal of regional lymph nodes was done under general anesthesia. The patient was then referred to Kathmandu Cancer Hospital for radiotherapy, 5 daily fractions a week fractionated for seven weeks, each session of 50 Gy.OUTCOMES AND FOLLOW UPThe patient is still being monitored, two years after the end of the treatment and she is not exhibiting any signs of recurrence at present. However, the patient presented with the signs of radiation mucositis. (Figure 6)DISCUSSIONAccording to the estimates from the GLOBOCAN project in 2018, there are at least 354,864 new cases of oral cancer (mostly SCC) worldwide each year, i.e., 2.0% of all malignancies [5]. It is approximated that carcinoma of the oral cavity in conjunction with lip cancer ranks sixth among all cancers in Nepal and fourth among cancers in men [6]. Gingival carcinoma represents a rare but distinct subgroup of OSCC. Carcinoma of the gingiva is an insidious disease that often lacks the clinical manifestation of the malignant tumor and hence is misdiagnosed as other inflammatory conditions of the periodontium, subsequently influencing the patient’s prognosis and chance for survival. Usually originating from keratinized mucosa in a posterior location, it frequently destroys the underlying bone, resulting in tooth mobility [7].Tobacco abuse, either in smoked or smokeless form, alcohol consumption, and betel nut chewing can be regarded as significant contributing factors to SCC, even though the exact etiology of this condition is unknown [4]. However, Yoon et al [8] and Meleti et al [9] stated that there is no strong correlation between gingival SCC and traditional risk factors. In contrast, Souza et al [10] have documented a strong correlation between smoking and alcohol intake and gingival SCC. The majority of case studies [3] have documented a predilection of gingival SCC for mandibular arches, however, Lubek et al. discovered nearly equal amounts of gingival lesions in both arches [11]. The average age of onset of gingival SCC is similar to that of other intra-oral SCC. Historically, it was considered as the disease of the elderly but there has been a recent shift in the prevalence of these lesions in younger patients who do not meet the established risk factors [12]. Since isolated cases of gingival SCC in pediatric patients have also been reported, clinicians should not discount the possibility of gingival SCC in this patient population [13].The diagnosis of gingival SCC is quite difficult due to its resemblance to other periodontal inflammatory conditions as well as to other pre-malignant conditions. In the present case, uniform white plaques seen on the vestibular area of the underlying tooth may be suggestive of homogenous leukoplakia, which has a very low malignant transformation rate. Brooks et al, in a case report, described a case of SCC of the gingiva in a 60-year-old female patient, with an unexpected clinical presentation. The patient displayed persistent gingival bleeding with a moderately inflamed and ulcerated border on the maxillary right molar region. She had previously experienced right-sided stage 2 breast cancer. An incisional biopsy was carried out after taking into account her medical history and the possibility of metastases. According to the histopathological analysis, the lesion was identified as a moderate to well-differentiated gingival SCC [4]. Another similar case was reported by Khan et al, where the clinical presentation of the patient was misleading giving the diagnosis of Necrotizing Ulcerative Periodontitis (NUP), yet the diagnosis of well-differentiated SCC was confirmed by the histopathological results [15].In cases of refractory chronic periodontal diseases, the clinician must be skeptical of any changes in the morphology of the gingiva, for instance, desquamations, ulcerations, papillae loss, and verrucous and hyperplastic growths, as these may be early clinical indicators of the upcoming malignancy. If suspicious gingival lesions remain after the etiological agents have been removed for longer than two weeks, a thorough history, clinical examination, and biopsy should be carried out for histopathological analysis in order to rule out malignancy and improve success and survival rates of the treatment.Therefore, when treating rare periodontal disorders, gingival SCC should always be taken into account as a differential diagnosis. In situations like these, periodontists can be lifesavers because they can help rule out this aggressive disease even in the absence of risk factors.Author ContributionsGitanjali Subedi – Conceptualization, Data curation, Methodology, Writing – original draftManoj Humagain – SupervisionArjun Hari Rijal – Validation, Writing – review and editingSimant Lamichhane – Writing – review and editingPratibha Poudel – InvestigationSachita Thapa - ResourcesREFERENCESCapote-Moreno A, Brabyn P, Muñoz-Guerra MF, et al. Oral squamous cell carcinoma: epidemiological study and risk factor assessment based on a 39-year series. Int J Oral Maxillofac Surg . 2020;49(12):1525-34.Sundermann BV, Uhlmann L, Hoffmann J, et al. The localization and risk factors of squamous cell carcinoma in the oral cavity: A retrospective study of 1501 cases. J Craniofac Surg . 2018;46(2):177-82.Niu LX, Feng ZE, Wang DC, et al. Prognostic factors in mandibular gingival squamous cell carcinoma: A 10-year retrospective study.Int J Oral Maxillofac Surg . 2017;46(2):137-43.Brooks JK, Kleinman JW, Lubek JE, et al. Gingival squamous cell carcinoma: An unexpected clincal presentation. Quintessence Int . 2019;50(1):50-7.Bray F, Ferlay J, Soerjomataram I, Siegel RL, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: Cancer J Clin . 2018;68(6):394-424.Gajurel R, Gautam DK, Pun CB, et al. Trends and clinicopathological characteristics of oral squamous cell carcinomas reported at a tertiary cancer hospital in Nepal during 1999 to 2009. Clin Exp Dent Res . 2020;6(3):356-62.Bharanidharan R, Dineshkumar T, Raghavendhar K, et al. Squamous cell carcinoma of the gingiva: A diagnostic enigma. J Oral Maxillofac Pathol . 2015;19(2):267.Yoon TY, Bhattacharyya I, Katz J, et al. Squamous cell carcinoma of the gingiva presenting as localized periodontal disease.Quintessence Int . 2007;38(2):97-102.Meleti M, Corcione L, Sesenna E, et al. Unusual presentation of primary squamous cell carcinoma involving the interdental papilla in a young woman. Br J Oral Maxillofac Surg. 2007; 45(5):420-2.Souza RP, Moreira PTB, Paes Junior AJO, et al. Gingival squamous cell carcinoma: imaging analysis of seven patients. Radiol Bras . 2003;36(4):225-7.Lubek J, El-Hakim M, Salama AR, et al. Gingival carcinoma: retrospective analysis of 72 patients and indications for elective neck dissection. Br J Oral Maxillofac Surg . 2011;49(3):182-5.Sultan N, Rao JR. Unusual presentation of primary mandibular gingival squamous cell‎ carcinoma in young male: A case report. J Oral Health Oral Epidemiol . 2015;4(2):107-10.Sidell D, Nabili V, Lai C, et al. Pediatric squamous cell carcinoma: case report and literature review. The Laryngoscope . 2009;119(8):1538-41.

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Clinical Pitfall Related to the Measuring of Serum Estradiol Concentrations Under Gel Transdermal Estrogen Replacement Therapy: A Case Report of Iatrogenic Primary Ovarian InsufficiencyTakeki Sato1, Masahito Tachibana1,2, Hiroaki Hiraga1, Emi Yokoyama1, Zen Watanabe1, and Masatoshi Saito1,2Department of Obstetrics and Gynecology, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai-shi, Miyagi 980-8574, JapanDepartment of Perinatology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai-shi, Miyagi 980-8574, Japan

Sense-B-noise is a rare cause of inappropriate shock (IAS) of subcutaneous implantable cardioverter defibrillator (S-ICD), which is an oversensing of primary and alternate vectors using the sense B and a factor of non-cardiac signal oversensing. The mechanism of sense-B-noise is unclear and considered to be a malfunction of the sense B circuit, including the ring and lead. We present a case of a 47-year-old man, who experienced IAS of S-ICD due to sense-B-noise followed by intense noise of primary and alternate vectors. This case implied that the mechanism of sense-B-noise may be an initial sign of malfunction of the sense B circuit.

Atrial esophageal fistula (AEF) is a rare but life-threatening complication of atrial fibrillation (AF) ablation, linked to thermal injuries by conventional radiofrequency (RF) and cryo-balloon (CB) ablation techniques. AEF risk can be mitigated by considering several measures such as monitoring esophageal luminal temperature, tailored power settings of ablation technique, mechanical displacement of esophagus, esophageal cooling, and alternative ablative techniques and energy sources. We review the current knowledge regarding AEF and esophageal thermal injuries as well as discussing the current research regarding a novel non-thermal, myocardial tissue-selective modality known as pulsed-field ablation (PFA) which may mitigate such risks. By inducing irreversible electroporation, PFA reduces thermal injury and demonstrates improved safety profiles, as evidenced by recent meta-analyses reporting zero esophageal injury and AEF cases. Additionally, the integration of 3D mapping systems with PFA has enhanced its procedural precision and accuracy as well as the ability to utilize real-time imaging. Despite these advances, challenges such as standardizing anesthesia protocols and tailoring energy settings remain. Our review suggests that PFA may reduce the risk of AEF from catheter ablation of AF. Although PFA may reduce the risk of any aberrant thermal injuries, studies report increased incidences of coronary vasospasms and hemolysis. Future long-term outcome studies should provide more information on possible adverse outcomes with PFA as well as tailoring the power settings of PFA.

This article develops a duality principle through a D.C. approach applicable to some originally non-convex primal variational formulations. More specifically, in a first step, we develop applications to a Ginzburg-Landau type equation. The results are obtained through basic tools of functional analysis, calculus of variations, duality and optimization theory in infinite dimensional spaces. It is worth emphasizing we have obtained a dual variational formulation which may be applied to a large class of similar models in the calculus of variations.

Background and Purpose: The endocannabinoid (eCB) system modulates many biological processes, including adult neurogenesis, emotional behaviour and stress-related signaling pathways. Intrinsic levels of eCB ligands, such as anandamide, are regulated in part, by fatty acid binding protein 5 (FABP5), a chaperone protein that transports anandamide for hydrolysis. Experimental Approach: Here, using pre-clinical rodent models, we examined the effects of pharmacological FABP5 inhibition on anxiety- and depressive-like behaviours and associated molecular signaling pathways, following exposure to chronic stress. In addition, we investigated the impacts of chronic stress on hippocampal neurogenesis and how FABP5 inhibition may modulate stress-induced deficits in hippocampal neurogenic mechanisms. Key Results: Remarkably, we report that anxiety- and depressive-like behaviours are strongly prevented by systemic FABP5 inhibition and associated with altered transcription of IGF-1, CB2 and GPR55 receptors as well as by altered phosphorylation of Erk1/2, Akt and p70S6 kinase pathways in the limbic circuitry. Finally, FABP5 inhibition potently blocked stress-induced reductions in hippocampal neurogenesis. Conclusions and Implications: These findings identify FABP5 inhibition as a promising pharmacotherapeutic candidate for stress-induced mood and anxiety symptoms.

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the intracellular accumulation of α-synuclein (α-syn) protein within Lewy bodies, which are hallmark neuropathological lesions of α-synucleinopathies. Network analysis, incorporating prior knowledge such as biological pathways and gene expression data from patients with PD, was used to identify the pharmaceutically active ingredients of MT101-5 and elucidate their mechanisms of action related to proteasome activation in PD. To validate the artificial intelligence (AI) model’s prediction that API-mediated α-syn aggregate clearance occurs through enhanced proteasome activity, we employed a reporter-based screening to assess proteasome function within the ubiquitin-proteasome system. Our findings demonstrated that diterpenes derived from Daphne Genkwa in MT101-5 inhibited α-syn fibril formation by restoring proteasome activation through Nurr1 activity. These results provide preliminary evidence supporting the therapeutic potential of the active ingredients in MT101-5 for the prevention or treatment of PD.

Abstract Background and Purpose Galanin receptor subtypes 1 (GALR1) and 2 (GALR2) are G protein-coupled receptors (GPCRs) that mediate galanin’s diverse physiological roles, including neurotransmission and neuronal modulation. Although both receptors share functional similarities, they exhibit distinct differences in signaling pathways. While previous studies have focused on galanin binding and G-protein selectivity, the role of plasma membrane-specific mechanisms, particularly cholesterol’s influence, remains unclear. This study investigates cholesterol’s role in regulating GALR1 and GALR2 trafficking and function in live cells. Experimental Approach We employed real-time fluorescence techniques—Fluorescence Correlation Spectroscopy (FCS), Fluorescence Cross-Correlation Spectroscopy (FCCS), and Fluorescence Recovery After Photobleaching (FRAP)—to assess receptor-ligand interactions and lateral mobility in PC12 cells expressing EGFP-tagged GALR1 or GALR2. Key Results Both receptors co-localized, co-trafficked, and internalized with galanin, with receptor-peptide complexes dissociating prior to lysosomal degradation. Cholesterol selectively restricted GALR1’s lateral diffusion and enhanced galanin binding and complex formation, while GALR2 remained unaffected. Interestingly, galanin binding relieved GALR1 from cholesterol-mediated restriction, increasing receptor mobility and suggesting a dynamic, cholesterol-dependent regulatory mechanism. Conclusions and Implications Cholesterol selectively modulates GALR1 trafficking and ligand interactions, while GALR2 operates independently of cholesterol, revealing distinct regulatory mechanisms for each receptor subtype. These findings provide new insights into the interplay between membrane composition and receptor function, with potential implications for developing targeted therapies for galanin-related disorders.

The extracellular amyloid plaques of β-amyloid (Aβ) peptides formed in the human brain are an important pathological hallmark of Alzheimer’s disease. There is evidence that pH affects the morphologies of fibrils and the kinetics of amyloid fibril formation. However, the underlying molecular mechanism is not well understood. In this study, as a first step to understand pH-modulated Aβ fibril formation, we investigated the conformations of Aβ(16-22) octamers by performing extensive all-atom replica exchange molecular dynamics simulations at both neutral and acidic pH. Our simulations showed that the residues Phe20 and Ala21 in the C terminal have higher β-sheet probability (78.8%, 55.8%) at acidic pH than (62.3%, 43.6%) at neutral pH. Out-of-register antiparallel β-strand alignments of the Aβ(16-22) peptide are predominantly in the 1-, 2- and 3-residue shifts at both pH conditions, which agrees well with solid-state NMR results on Aβ peptides. We also found that there are multiple in-register and out-of-register parallel β-strand alignments under both pH conditions. However, the pH conditions affect the probability of β-strand alignments for the Aβ(16-22) peptide, and the residue-residue interaction of bilayer β-sheet and β-barrel are different at different pH conditions. Our analysis showed that the electrostatic interactions among peptides are much stronger at neutral pH than at acidic pH, while the vdW interactions are slightly stronger at acidic pH than at neutral pH. These results provide atomistic insight into the early stage of aggregation of β-amyloid (Aβ) peptides at acidic and neutral pH conditions.

Background: Bronchopulmonary Dysplasia is a relatively common disorder affecting preterm infants, impacting their health and future development. Although machine learning methodologies serve as valuable tools for making predictions and extracting biomedical insights, their use for in-depth analysis and prediction of diseases remains limited. In this study, we employed machine learning techniques to identify key genes associated with Bronchopulmonary Dysplasia and their correlation with immune cells. Method: We screened a dataset of premature infants with Bronchopulmonary Dysplasia and downloaded the related datasets from the GEO database. Subsequently, we conducted an analysis of differentially expressed genes (DEGs). With Gene Ontology (GO) annotation, we classified DEGs according to the official classification and performed GO functional enrichment using the phyper function of R. KEGG pathway analysis was also conducted through pathway functional enrichment employing the same R function. We utilized Weighted Gene Co‐expression Network Analysis (WCGNA) to identify co‐expression gene modules, explore the relationship between the gene network and phenotype, and pinpoint key genes in the network. Genes were then fitted using the Least Absolute Shrinkage and Selection Operator (Lasso),Support Vector Machine (SVM) and Random Forest analysis. Following the characterization of differentially expressed genes, we employed Gene Set Pathway Enrichment analyses (GSEA) to identify enriched signaling pathways. Finally, the infiltration of immune cells was classified using CIBERSORT. Results: Our analysis of GSE32472 identified a total of 273 differentially expressed genes (DEGs). When applying the WGCNA method to our dataset, we categorized 20002 gene expression traits into 21 modules. Remarkably, the red module showed a significant correlation with Bronchopulmonary Dysplasia (correlation=-0.6, p<0.0001). We utilized LASSO, SVM, and random forest algorithms to select signature genes, which included CCDC141, CHI3L2, PDLIM7, and RIMKLB. The receiver operating characteristic (ROC) curves for these signature genes were 0.928（95% CI: 0.761−0.969）, 0.880（95% CI: 0.803−0.971）, 0.900（95% CI: 0.841−0.986）, and 0.880（95% CI: 0.793−0.975）, respectively, and this was confirmed using an external dataset from GSE108754. Furthermore, to verify whether these selected genes are highly expressed in the mother and thus contribute to the newborn’s susceptibility to BPD, we used GSE188944 as a validation set. GSEA analysis suggested that these signature genes are involved in the spliceosome, sulfur metabolism, RNA degradation, aminoacyl-tRNA biosynthesis, T cell receptor signaling pathway, maturity onset diabetes of the young, PPAR signaling pathway, and glycosaminoglycan degradation, all of which are positively correlated. Conclusion: CCDC141, CHI3L2, PDLIM7, and RIMKLB demonstrated significant diagnostic advantages for neonatal bronchopulmonary dysplasia and played a crucial role in immune cell infiltration.

Objective: To describe ventilation strategies for weaning patients from prolonged mechanical ventilation (PMV) in Pediatric Intensive Care Units (PICUs). Method: Conducted a retrospective study across eleven PICUs in mainland China from January 1, 2021, to December 31, 2022. Results: 234 patients diagnosed with PMV were included in the study. Weaning Outcomes: 42.3% (99 patients) successfully weaned and extubated. 15.8% (37 patients) required only a tracheostomy. 9.8% (23 patients) needed non-invasive ventilation. 32.1% (75 patients) continued to require mechanical ventilation. 34.2% (80 patients) on invasive pressure control mode at PMV diagnosis. Pressure control was the most commonly used method. Synchronized intermittent mandatory ventilation (SIMV) used by 30.4% (71 patients). Pressure support ventilation (PSV) used by 5.1% (12 patients). 63.2% (148 patients) received physiotherapy. 44.9% (105 patients) received cough augmentation techniques. 26.9% (63 patients) underwent tracheostomy after an average of 29 days of invasive mechanical ventilation. Higher fraction of inspired oxygen (FiO 2) linked to weaning failure (HR=1.025). Sedation on PMV diagnosis day linked to weaning success (HR=0.392). Presence of tracheostomy associated with weaning success (HR=0.435). Patients with lower airway diseases had better weaning outcomes compared to those with central nervous system diseases (HR=0.484). Conclusion: Pressure control ventilation was the initial mode; SIMV and PSV were preferred for weaning. Higher FiO 2 on the day of the PMV diagnosis was associated with weaning failure, while sedation and tracheostomy were likely linked to weaning success. Lower airway diseases showing better outcomes than central nervous system diseases.